This application addresses broad Challenge Area (04) Clinical Research and specific Challenge Topic, 04-HL-115: Treatment of stenosed coronary arteries with hybrid coronary revascularization versus multi-vessel percutaneous coronary intervention with drug eluting stents (DES). This proposal is for a planning grant to complete the remaining steps needed to start a pivotal trial evaluating the effectiveness of Hybrid coronary revascularization (HCR). The enormous and increasing prevalence of coronary artery disease (CAD), ongoing innovation in coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and medical therapy, as well as the costs of revascularization have stimulated rising interest in optimal techniques and indications for coronary revascularization. Hybrid coronary revascularization, which combines CABG and PCI, offers potential advantages beyond CABG or PCI alone, and could have a major impact on the health care system. The ability to deliver a new therapy for CAD that provides durability, but without the obligatory trauma and prolonged recovery time characteristic of conventional CABG, would be a major advance in the field of cardiovascular medicine. While the HCR approach has been steadily growing in many heart centers in the US, the efficacy and safety of HCR rests upon data obtained through small observational studies. Preliminary observational data suggest that HCR has the potential to disseminate widely and become the third major interventional alternative for patients with multi-vessel CAD. However, without a rigorously designed clinical trial there is insufficient evidence to guide ongoing dissemination of this potentially important procedure for a major patient population. This planning grant application will provide the support for the organization of activities critical for the successful implementation of a large-scale randomized trial comparing the effectiveness and safety of HCR versus multi-vessel PCI with DES in patients with three-vessel CAD. The investigators of this proposal build on the already established infrastructure of the Cardiothoracic Surgical Trials Network ([CTSN] (http://www.ctsurgerynet.org): an NHLBI-funded Network of 10 clinical centers and a Data Coordinating Center] and several additional prominent clinical centers in the field of HCR. The key aims of this proposal include: (1) Finalizing the design and protocol for the pivotal trial, (2) Conducting an observational study that will inform the pivotal trial design, and (3) Expanding the infrastructure of investigators, committees and the data coordinating center (DCC) to execute the pivotal trial. These activities should culminate within 18 months in a grant application for the pivotal trial, which could start immediately following this planning phase. The results of the proposed clinical trial will fundamentally change the management of coronary artery disease patients. This trial, which will support faculty and coordinators in numerous clinical centers across the country and at the DCC, will provide evidence to guide and improve treatment decisions and optimize utilization of health care resources through data on the cost-effectiveness of alternative treatment options. The economic impact of the proposed research, however, is much broader than improving the effectiveness and efficiency of treating the still expanding disease population. Coronary artery disease therapeutics is a field with a high degree of innovation. The knowledge generated by the trial will provide feedback to an R&D enterprise of scientists, engineers, and clinicians in universities and industrial firms, which will allow them to develop new technologies and refine existing ones for the treatment of CAD. The ability to deliver hybrid coronary revascularization (HCR) as a new, scientifically-validated approach for CAD would be a major advance in cardiovascular medicine and a major impact on public health. Moreover, HCR is likely to bridge the divide in treatment philosophies and approaches that exist between cardiologists and cardiac surgeons. Collaboration rather than competition between these specialties will ultimately benefit patients, hospitals, payers and healthcare providers.